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Overexpression of fibulin-5 in retinal pigment epithelial cells inhibits cell proliferation and migration and downregulates VEGF, CXCR4, and TGFB1 expression in cocultured choroidal endothelial cells.
Curr Eye Res. 2012 Jun; 37(6):540-8.CE

Abstract

PURPOSE OF THE STUDY

Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss. Fibulin-5 (FBLN5) plays a pleiotropic role in the pathogenesis of AMD. We examined whether the in vitro overexpression of FBLN5 in retinal pigment epithelial (RPE) cells alters the proliferation and migration of cocultured choroidal endothelial cells (CECs) and explored the possible mechanisms involved.

MATERIALS AND METHODS

A recombinant lentiviral vector carrying the Fbln5 gene was generated to transduce rat RPE cells. The expression of FBLN5 in transduced RPE cells was detected by quantitative real-time PCR and Western blot. The transduced RPE cells were then cocultured with rhesus macaque CECs in a Transwell coculture system. The impact of overexpression of FBLN5 in RPE cells on CEC proliferation and migration was assessed, as well as the impact on the mRNA expressions of vascular endothelial growth factor (VEGF), C-X-C chemokine receptor type 4 (CXCR4), and transforming growth factor β1 (TGFB1).

RESULTS

Our results showed that a recombinant lentivirus carrying the Fbln5 gene, which could induce overexpression of FBLN5 in RPE cells, was successfully generated. Overexpression of FBLN5 in RPE cells inhibited cell proliferation and migration and downregulated the mRNA expressions of VEGF, CXCR4, and TGFB1 in cocultured CECs.

CONCLUSIONS

These findings suggest that FBLN5 may interfere with choroidal neovascularization by downregulating VEGF, CXCR4, and TGFB1 expression and inhibiting CEC proliferation and invasion, intensifying interest in FBLN5 as a target for therapeutic intervention in neovascular AMD.

Authors+Show Affiliations

Southwest Hospital, Southwest Eye Hospital, Third Military Medical University, Chongqing, P. R. China.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22369482

Citation

Li, Fuliang, et al. "Overexpression of Fibulin-5 in Retinal Pigment Epithelial Cells Inhibits Cell Proliferation and Migration and Downregulates VEGF, CXCR4, and TGFB1 Expression in Cocultured Choroidal Endothelial Cells." Current Eye Research, vol. 37, no. 6, 2012, pp. 540-8.
Li F, Xu H, Zeng Y, et al. Overexpression of fibulin-5 in retinal pigment epithelial cells inhibits cell proliferation and migration and downregulates VEGF, CXCR4, and TGFB1 expression in cocultured choroidal endothelial cells. Curr Eye Res. 2012;37(6):540-8.
Li, F., Xu, H., Zeng, Y., & Yin, Z. Q. (2012). Overexpression of fibulin-5 in retinal pigment epithelial cells inhibits cell proliferation and migration and downregulates VEGF, CXCR4, and TGFB1 expression in cocultured choroidal endothelial cells. Current Eye Research, 37(6), 540-8. https://doi.org/10.3109/02713683.2012.665561
Li F, et al. Overexpression of Fibulin-5 in Retinal Pigment Epithelial Cells Inhibits Cell Proliferation and Migration and Downregulates VEGF, CXCR4, and TGFB1 Expression in Cocultured Choroidal Endothelial Cells. Curr Eye Res. 2012;37(6):540-8. PubMed PMID: 22369482.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Overexpression of fibulin-5 in retinal pigment epithelial cells inhibits cell proliferation and migration and downregulates VEGF, CXCR4, and TGFB1 expression in cocultured choroidal endothelial cells. AU - Li,Fuliang, AU - Xu,Haiwei, AU - Zeng,Yuxiao, AU - Yin,Zheng Qin, Y1 - 2012/02/28/ PY - 2012/2/29/entrez PY - 2012/3/1/pubmed PY - 2012/8/10/medline SP - 540 EP - 8 JF - Current eye research JO - Curr Eye Res VL - 37 IS - 6 N2 - PURPOSE OF THE STUDY: Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss. Fibulin-5 (FBLN5) plays a pleiotropic role in the pathogenesis of AMD. We examined whether the in vitro overexpression of FBLN5 in retinal pigment epithelial (RPE) cells alters the proliferation and migration of cocultured choroidal endothelial cells (CECs) and explored the possible mechanisms involved. MATERIALS AND METHODS: A recombinant lentiviral vector carrying the Fbln5 gene was generated to transduce rat RPE cells. The expression of FBLN5 in transduced RPE cells was detected by quantitative real-time PCR and Western blot. The transduced RPE cells were then cocultured with rhesus macaque CECs in a Transwell coculture system. The impact of overexpression of FBLN5 in RPE cells on CEC proliferation and migration was assessed, as well as the impact on the mRNA expressions of vascular endothelial growth factor (VEGF), C-X-C chemokine receptor type 4 (CXCR4), and transforming growth factor β1 (TGFB1). RESULTS: Our results showed that a recombinant lentivirus carrying the Fbln5 gene, which could induce overexpression of FBLN5 in RPE cells, was successfully generated. Overexpression of FBLN5 in RPE cells inhibited cell proliferation and migration and downregulated the mRNA expressions of VEGF, CXCR4, and TGFB1 in cocultured CECs. CONCLUSIONS: These findings suggest that FBLN5 may interfere with choroidal neovascularization by downregulating VEGF, CXCR4, and TGFB1 expression and inhibiting CEC proliferation and invasion, intensifying interest in FBLN5 as a target for therapeutic intervention in neovascular AMD. SN - 1460-2202 UR - https://www.unboundmedicine.com/medline/citation/22369482/Overexpression_of_fibulin_5_in_retinal_pigment_epithelial_cells_inhibits_cell_proliferation_and_migration_and_downregulates_VEGF_CXCR4_and_TGFB1_expression_in_cocultured_choroidal_endothelial_cells_ L2 - https://www.tandfonline.com/doi/full/10.3109/02713683.2012.665561 DB - PRIME DP - Unbound Medicine ER -